1. Th2 cell differentiation from naive<scp>CD</scp>4+T cells is enhanced by autocrine<scp>CC</scp>chemokines in atopic diseases
- Author
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Yasutsugu Fukushima, Kazuhiro Kurasawa, Masafumi Arima, Takeshi Fukuda, Tatsuo Yukawa, Ayae Tanaka, Tomoyuki Miyao, and Hirokuni Hirata
- Subjects
0301 basic medicine ,Chemokine ,Thymic stromal lymphopoietin ,biology ,business.industry ,Cellular differentiation ,Immunology ,CCR4 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,biology.protein ,Immunology and Allergy ,CCL17 ,Medicine ,business ,CC chemokine receptors ,Autocrine signalling ,CCL22 - Abstract
Background Chemokines are involved not only in regulating leucocyte recruitment, but also in other activities. However, functions other than cell recruitment remain poorly understood. We have already shown that the production of CC chemokine ligand (CCL)17 and CCL22 by antigen-stimulated naive CD4+ T cells was higher in asthmatic patients than in healthy controls. However, the role of these chemokines in stimulated naive CD4+ T cells remains unclear. Objective To clarify the biological function of CCL17 and CCL22 on naive CD4+ T, we examined effects of these two chemokines on naive CD4+ T cells expressing CC chemokine receptor (CCR)4 (a receptor for CCL17 and CCL22) during differentiation of Th2 cells in asthmatic patients as allergic subjects. Methods Naive CD4+ T cells were prepared from healthy controls and patients with asthma. We analysed effect of CCL17 and CCL22, and blocking their receptor on differentiation of Th2 cells. Results Production of CCL17 and CCL22 by activated naive CD4+ T cells under Th2 condition was much more in asthmatic patients than in healthy controls. Proliferation and survival of the Th2 differentiating cells and restimulation-induced IL-4 production were much greater in asthmatic patients than in healthy controls. These cell biological phenomena were inhibited by blockade of CCR4. The biological effects of exogenous CCL17 and CCL22 were apparently observed in both healthy controls and asthmatic patients. The effectiveness of these chemokines on naive CD4+ T cells from healthy controls was stronger than those from asthmatic patients. We found that thymic stromal lymphopoietin (TSLP), a Th2 promoting chemokine, is involved in the activation of CD4+ naive T cells via production of CCL17 and CCL22. Conclusions and clinical relevance These data suggest that CCL17 and CCL22 produced by TSLP-primed naive CD4+ T cells in asthma might contribute to an increase in Th2 cells via autocrine loops.
- Published
- 2018
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